Glioblastoma, Glioblastoma With Primitive Neuronal Component, Gliosarcoma, Malignant Glioma, Oligodendroglial Component Present
Conditions
Brief summary
This phase II trial studies how well whole brain radiation therapy works with standard temozolomide chemo-radiotherapy and plerixafor in treating patients with glioblastoma (brain tumor). Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Plerixafor is a drug that may prevent recurrence of glioblastoma after radiation treatment. Giving whole brain radiation therapy with standard temozolomide chemo-radiotherapy and plerixafor may work better in treating patients with glioblastoma.
Detailed description
PRIMARY OBJECTIVES: I. The primary purpose of this Phase II study is to evaluate the efficacy of Plerixafor administered with a modified radiation regimen that includes a component of WBRT. The primary endpoint is 6-month progression free survival post initiation of Chemoradiation. SECONDARY OBJECTIVES: I. To assess the median survival of patients treated with continuous infusion plerixafor/WBRT. II. To assess the toxicities both short and long term of continuous infusion plerixafor/WBRT. III. To assess the patterns of failure (in and out of irradiated brain field, out of brain) of continuous infusion plerixafor/WBRT. OUTLINE: After completion maximal safe surgical resection, patients undergo radiation therapy for 42 days, initiating whole brain radiation therapy at day 21 (dose 16 of radiation therapy) and receive temozolomide daily on days 1-42. Beginning 7 days before the completion of whole brain radiation therapy, patients receive plerixafor by continuous infusion on days 1-28. Beginning 1 week after completion of plerixafor infusion and 35 days after completion of whole brain radiation therapy, patients receive temozolomide monthly for 6-12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for adverse events for 30 days after the last dose of Plerixafor and then every 12 weeks for 5 years for survival follow-up.
Interventions
DRUGPlerixafor
Plerixafor will be administered via infusion at 400 micrograms per kilogram per day for four weeks beginning one week before the end of radiation
DRUGTemozolomide
Temozolomide (TMZ) will be administered concurrently with the radiation for 42 days and 6-12 cycles of monthly adjuvant Temozolomide (TMZ) after completion of Plerixafor infusion.
RADIATIONWhole-Brain Radiotherapy (WBRT)
Undergo Whole brain radiotherapy (WBRT) - Radiotherapy consists of 30 Gy in 15 fractions of whole brain radiations
RADIATIONRadiation Therapy
Radiotherapy consists of 30 Gy in 15 fractions
Sponsors
Sanofi
Lawrence D Recht
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients must have tissue confirmation of high grade (World Health Organization (WHO) grade IV) glioma including but not limited to glioblastoma, gliosarcoma, glioblastoma with oligodendroglial features, glioblastoma with primitive neuroectodermal tumor (PNET) features. * The patient must have post-operative contrast enhanced imaging (computed tomography \[CT\] or magnetic resonance imaging \[MRI\]) unless only biopsy performed. For patients having biopsy alone, post-operative imaging is not routinely obtained and therefore the preoperative study will serve as baseline. * Patient should have surgery (biopsy, partial resection or gross total resection) and no additional anti-cancer therapy except the chemo-radiation as specified in the protocol. * Patients must have Karnofsky performance score \>= 60. * Absolute neutrophil count (ANC) \>= 1500 (at time of screening). * Platelets \>= 100,000 ml (at time of screening). * Serum creatinine =\< 1.5mg/dl (at time of screening). * Creatinine (Cr) clearance should be \> 50 mL/min (at time of screening). * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 times the upper limit of normal (at time of screening). * If female of childbearing potential, negative pregnancy test (at time of screening). * The patient or his/her legal representative must have the ability to understand and willingness to sign a written informed consent document. * Patient agrees to use an effective method of contraception (hormonal or two barrier methods) while on study and for at least 3 months following the plerixafor infusion.
Exclusion criteria
* Prior or concurrent treatment with Avastin (bevacizumab). * Prior exposure to plerixafor. * Prior use of other investigational agents to treat the brain tumor. * Recent history of myocardial infarct (less than 3 months) or history of active angina. * Prior malignancy except for non-melanoma skin cancer and carcinoma in situ (of the cervix or bladder), unless diagnosed and definitively treated more than 3 years prior to 1st dose of investigational drug. * Prior sensitivity to plerixafor. * Pregnant or patients who are breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Progression Free Survival Participants (PFS) at Six Months | 6 months | Proportion of Progression free survival will be measured at 6 months post initiation of chemoradiation. Simon 2-stage design will be use to assess progression-free survival. Will be computed from start of induction therapy and summarized with Kaplan-Meier estimates. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Survival | up to 31 months | Median survival will be assessed at 31 months of subjects who have completed the 28 day Plerixafor infusion. Will be computed from start of induction therapy and summarized with Kaplan-Meier estimates. |
| Toxicity Associated With Plerixafor/WBRT | 30 days | Incidence of adverse events will be graded and recorded per Common Terminology Criteria for Adverse Events version 5.0. Will assess reported toxicities up until 30 days of treatment. The number of participants experiencing adverse events, including qualifying dose limiting toxicities (DLTs) will be tabulated by attribution (Unrelated, Unlikely to be related, Definitely related) and severity. |
| Patterns of Treatment Failure | 5 years | Patterns of Failure in patients receiving Whole Brain Radiotherapy + Plerixafor + Chemoradiotherapy was assessed by determining the out-of-field occurrence or occurrence outside of the brain over time. Local treatment failure was defined as within the 95% isodose region. Out-of-field occurrence is defined by any treatment failure observed outside treatment area. |
Countries
United States
Participant flow
Pre-assignment details
21 participants signed informed consent; 17 participants were allocated to treatment; 2 patients still in follow up
Participants by arm
| Arm | Count |
|---|---|
| Whole Brain Radiotherapy + Plerixafor +Chemoradiotherapy After completion maximal safe surgical resection, patients undergo radiation therapy for 42 days, initiating whole brain radiation therapy at day 21 (dose 16 of radiation therapy) and receive temozolomide daily on days 1 to 42. Beginning 7 days before the completion of whole brain radiation therapy, patients receive plerixafor by continuous infusion on days to 1 to 28. Beginning 1 week after completion of plerixafor infusion and 35 days after completion of whole brain radiation therapy, patients receive temozolomide monthly for 6 to 12 courses in the absence of disease progression or unacceptable toxicity. | 17 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 15 |
| Overall Study | In follow up | 2 |
Baseline characteristics
| Characteristic | Whole Brain Radiotherapy + Plerixafor +Chemoradiotherapy |
|---|---|
| Age, Customized 18 to 30 years | 1 Participants |
| Age, Customized 31 to 39 years | 1 Participants |
| Age, Customized 40 to 49 years | 3 Participants |
| Age, Customized 50 to 59 years | 6 Participants |
| Age, Customized 60 to 69 years | 4 Participants |
| Age, Customized 70 to 79 years | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Region of Enrollment United States | 17 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 15 / 17 |
| other Total, other adverse events | 16 / 17 |
| serious Total, serious adverse events | 3 / 17 |
Outcome results
Primary
Proportion of Progression Free Survival Participants (PFS) at Six Months
Proportion of Progression free survival will be measured at 6 months post initiation of chemoradiation. Simon 2-stage design will be use to assess progression-free survival. Will be computed from start of induction therapy and summarized with Kaplan-Meier estimates.
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Whole Brain Radiotherapy + Plerixafor +Chemoradiotherapy | Proportion of Progression Free Survival Participants (PFS) at Six Months | 0.786 Proportion of participants |
Secondary
Median Survival
Median survival will be assessed at 31 months of subjects who have completed the 28 day Plerixafor infusion. Will be computed from start of induction therapy and summarized with Kaplan-Meier estimates.
Time frame: up to 31 months
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Whole Brain Radiotherapy + Plerixafor +Chemoradiotherapy | Median Survival | 398 days | Standard Error 0.134 |
Secondary
Patterns of Treatment Failure
Patterns of Failure in patients receiving Whole Brain Radiotherapy + Plerixafor + Chemoradiotherapy was assessed by determining the out-of-field occurrence or occurrence outside of the brain over time. Local treatment failure was defined as within the 95% isodose region. Out-of-field occurrence is defined by any treatment failure observed outside treatment area.
Time frame: 5 years
Population: Participants with available scan data were included in the analysis
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Whole Brain Radiotherapy + Plerixafor +Chemoradiotherapy | Patterns of Treatment Failure | In Field Occurrence | 12 Participants |
| Whole Brain Radiotherapy + Plerixafor +Chemoradiotherapy | Patterns of Treatment Failure | Out-of-field Occurrence | 2 Participants |
Secondary
Toxicity Associated With Plerixafor/WBRT
Incidence of adverse events will be graded and recorded per Common Terminology Criteria for Adverse Events version 5.0. Will assess reported toxicities up until 30 days of treatment. The number of participants experiencing adverse events, including qualifying dose limiting toxicities (DLTs) will be tabulated by attribution (Unrelated, Unlikely to be related, Definitely related) and severity.
Time frame: 30 days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Whole Brain Radiotherapy + Plerixafor +Chemoradiotherapy | Toxicity Associated With Plerixafor/WBRT | Grade 3 or higher AE | 3 Participants |
| Whole Brain Radiotherapy + Plerixafor +Chemoradiotherapy | Toxicity Associated With Plerixafor/WBRT | Related to WBRT treatment | 1 Participants |
| Whole Brain Radiotherapy + Plerixafor +Chemoradiotherapy | Toxicity Associated With Plerixafor/WBRT | Related to Plerixafor treatment | 0 Participants |